摘要目的:探讨程序性死亡配体1(PD-L1)表达水平对转移性肾细胞癌患者预后的预测价值。方法:回顾性分析北京肿瘤医院2014年1月至2016年4月收治的61例转移性肾细胞癌患者的临床病理资料和生存资料。男46例，女15例。中位年龄56(29~75)岁，其中≤60岁41例，>60岁20例。患者行系统治疗前，单个器官转移36例(59.0%)，≥2个器官转移25例(41.0%)；肺转移17例(27.9%)，肝转移54例(88.5%)。乳酸脱氢酶(LDH)正常52例，异常4例。MSKCC危险分层(共57例)低危组34例(59.6%)，中危组23例(40.4%)。6例(9.8%)初诊时即存在远处转移，其中4例接受原发灶减瘤术；余55例接受根治性肾切除术。采用免疫组化染色方法检测患者肿瘤组织的PD-L1表达水平，将肿瘤细胞膜检测到PD-L1染色≥1%定义为PD-L1阳性表达。分析PD-L1表达水平与临床病理特点的相关性，采用Kaplan-Meier法和log-rank检验比较不同临床病理特点亚组的无病生存时间(DFS)和总生存时间(OS)的差异。采用Cox比例风险回归模型进行生存数据的多因素分析。结果:本组61例术后病理诊断为透明细胞癌53例、乳头状肾细胞癌3例、集合管癌1例、易位相关性肾细胞癌2例、未分类2例。WHO/ISUP核分级(共52例)为1~4级分别为4例、20例、19例、9例。T 1期、T 2期、T 3期、T 4期(共60例)分别为26例、12例、20例、2例。淋巴结阳性5例，阴性56例。TNM分期Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为20例、11例、21例、8例。61例的PD-L1阳性表达率为24.6%(15/61)。WHO/ISUP核分级1~4级的PD-L1阳性表达率分别为0、5.0%(1/20)、31.6%(6/19)、44.4%(4/9)，差异有统计学意义( P=0.029)；随WHO/ISUP核分级的增加，PD-L1阳性表达率升高，两者间存在线性相关( P=0.006)。基线LDH水平正常组和异常组的PD-L1阳性表达率分别为19.2%(10/52)和75.0%(3/4)，差异有统计学意义( P=0.035)。DFS的单因素分析结果显示，PD-L1( P=0.045)、年龄( P=0.014)、WHO/ISUP核分级( P<0.001)、T分期( P=0.015)、N分期( P=0.026)、TNM分期( P=0.005)与DFS相关；多因素分析结果显示仅WHO/ISUP核分级为DFS的独立预后因素( HR=1.8，95% CI 1.1~2.9， P=0.018)。单因素( P=0.154)和多因素( P=0.902)分析结果均显示，PD-L1不是转移性肾细胞癌患者OS的预后因素。OS的独立预后因素包括：WHO/ISUP核分级( HR=3.0，95% CI 1.1~8.0， P=0.033)和MSKCC危险分层( HR=5.9，95% CI 1.2~29.7， P=0.03)。 结论:转移性肾细胞癌患者WHO/ISUP核分级越高，PD-L1阳性表达率越高。PD-L1阳性表达并不是转移性肾细胞癌患者DFS和OS的独立预后因素。

abstractsObjective:To explore the prognostic value of PD-L1 expression level in patients with metastatic renal cell carcinoma (mRCC).Methods:The clinicopathological and survival data of patients with mRCC in our hospital from Jan 2014 to Apr 2016 were retrospectively analyzed including 46 males and 15 females. The median age of these patients was 56 years(range: 29-75 years), with 41 patients ≤60 years and 20 patients >60 years. The baseline data before the systemic therapy showed 36 patients(59.0%)had 1 metastatic organ and 25 patients (41.0%) had equal or more than 2 organs to be metastasized. Among them, 17 patients(27.9%)had lung metastasis and 54 patients(88.5%)had liver metastasis. Abnormal baseline LDH occurred in 4 patients and 52 patients had normal LDH. Favorite and intermediate risk patients categorized by MSKCC risk stratification accounted for 59.6%(34 patients)and 40.4%(23 patients), respectively. Six patients(9.8%)experienced distant metastasis at initial diagnosis, with 4 of them undergoing primary site resection, and the other 55 patients undergoing radical nephrectomy. PD-L1 expression was detected by the immunohistochemical staining method. PD-L1 staining rate ≥1% detected on the tumor cell membrane was defined as positive expression. The correlation between PD-L1 expression and clinicopathological characteristics were compared. Kaplan-Meier method and log-rank test were used to compare the differences about DFS and OS under different factors. Cox proportional hazards regression model is used for multivariable analysis of survival data.Results:The detailed pathological types of the 61 patients with renal cell carcinoma were classified as 53 clear cell carcinomas, 3 papillary carcinomas, 1 collecting duct carcinoma, 2 translocation renal cell carcinomas and 2 being unclassified. There were 4, 20, 19 and 9 patients categorized as WHO/ISUP nuclear grade 1, 2, 3 and 4, and 26, 12, 20 and 2 patients were categorized as T 1, T 2, T 3 and T 4 stage, respectively. Five patients had regional lymph node metastasis(N+), and the other 56 patients had no regional lymph node metastasis(N-). The numbers of patients categorized as stage Ⅰ, Ⅱ, Ⅲ and Ⅳ diseases according to TNM staging system were 20, 11, 21 and 8, respectively. The total PD-L1 positive rate was 24.6%(15/61). The corresponding PD-L1 expression rate of patients with WHO/ISUP nuclear grade 1-4 were 0(0 patient), 5.0%(1 patient), 31.6%(6 patients)and 44.4%(4 patients), respectively; With the increasing WHO/ISUP nuclear grade, the positive rate of PD-L1 gradually escalated with a linear correlation ( P=0.006). The PD-L1 expression of the normal and abnormal LDH group were 19.2%(10 patients)and 75.0%(3 patients), respectively, with significant difference( P=0.035). Univariate analysis of disease-free survival time(DFS)showed that the prognostic factors include PD-L1( P=0.045), age group( P=0.014), WHO/ISUP nuclear grade( P<0.001), T stage( P=0.015), N stage( P=0.026)and TNM stage( P=0.005). However multivariate analysis only suggested WHO/ISUP nuclear grade as the independent prognostic factors for DFS( HR=1.8, 95% CI 1.1-2.9, P=0.018). Either in univariate or multivariate analysis, PD-L1 was not a prognostic factor for overall survival (OS)of mRCC patients(univariate analysis: P=0.154; multivariate analysis: P=0.902). The independent prognostic factors of OS include WHO/ISUP nuclear grade( HR=3.0, 95% CI 1.1-8.0, P=0.033)and MSKCC risk stratification( HR=5.9, 95% CI 1.2-29.7, P=0.03). Conclusions:This study showed that the higher the WHO/ISUP nuclear grade of patients with mRCC, the higher the positive rate of PD-L1. PD-L1 expression was not the independent prognostic factor for DFS or OS of mRCC.